Noncanonical Neural-Hemodynamic Coupling by Default and in Schizophrenia

Neuroimaging methods rely on models of neurovascular coupling that assume hemodynamic responses are canonical, evolving seconds after changes in neural activity. However, emerging evidence reveals noncanonical blood oxygen level-dependent (BOLD) responses that are delayed under stress and aberrant in neuropsychiatric conditions.

We simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging data in people with schizophrenia (n = 57) and psychiatrically unaffected participants (n = 46) during a resting-state paradigm. We focused on alpha band power to examine correlations with voxelwise, time-lagged BOLD signals as a dynamic measure of EEG-BOLD coupling.

We found pronounced diversity in the temporal profile of alpha-BOLD coupling across the brain. This included early coupling (0-2 seconds BOLD lag) for more posterior regions of the default mode network (DMN), thalamus, and brainstem. Anterior regions of the DMN showed coupling at more canonical lags (4-6 seconds), although some participants showed greater than expected lags associated with self-reported measures of stress and there were greater lag scores in participants with schizophrenia. Overall, noncanonical alpha-BOLD coupling is widespread across the DMN and other noncortical regions and is delayed in people with schizophrenia.

These findings suggest that hemodynamic signals are dynamically coupled to ongoing neural activity across distributed networks and that the hemoneural lag may be associated with subjective arousal or stress. Our work highlights the need for more studies of neurovascular coupling in psychiatric conditions.